From the late 1970s, cryoenergy has been used in the cardiovascular system starting from, for example, 1977 when it was used to surgically treat cardiac arrhythmias. Over the ensuing years it became widely recognized that cryoenergy was the energy source of choice when working in the heart. Its safety and efficacy was unsurpassed as surgeons were able to ablate delicate cardiac structures such as the A-V node, pulmonary veins and delicate peri-nodal atrial tissue without concern for thrombosis, perforation or other adverse events.
More recently, researchers have started investigating the use of cryoenergy in the vascular system as a method to treat calcified plaque. Clinical data published by Laird et. al. “Cryoplasty for the Treatment of Femoropopliteal Arterial Disease: Extended Follow-up Results” J ENDOVASC THE 2006; 13 (Suppl II): II-52-II-59 has shown that cryoenergy achieves good clinical results when used in highly stenosed vessels of the peripheral vasculature.
Much of this previous work has been in treating calcified plaque in patients with calcified highly stenosed vessels (>70% stenosis) as an alternative to drugs, balloon angioplasty, stents or other conventionally used therapies.
Cryoenergy is typically applied to a vessel using a balloon based catheter, in which a refrigerant is used to expand a balloon into contact with a target. The temperatures used in treating such calcified highly stenosed blood vessels range from −10° C. to −20° C. (263K to 253K) and are generally warmer than those used in the ablation field (such as those used to treat arrhythmia or for cancer tumor ablation) where refrigerant temperatures will generally be colder than −70° C. (203K). Typically, the pressure in the balloon will be above 5 atmospheres (ATM), 507 kPa, as the goal of the therapy is to force open critically stenosed calcified vessels.
There has also been some interest in using cryoenergy on non-critically stenosed plaque typical of so called vulnerable or unstable plaque, as exemplified by U.S. Pat. Nos. 6,673,066, 6,602,246 and 6,955,174. Vulnerable plaque, or unstable plaque, may be defined as a non-flow limiting plaque which is lipid rich with a thin cap fibroatheroma. For the purposes of this document the terms vulnerable and unstable plaque are used interchangeably.
When these plaques rupture, a thrombus forms and causes a heart attack. A discussion, description and characteristics of these types of plaques is reviewed in Libby, “Atherosclerosis: The New View” Scientific American, May 2002, pg. 47. In some early work, the biological effect was poorly understood and improperly described as, for example, in U.S. Pat. No. 6,955,174 where cryotherapy treatment is described which “inhibits release of the retained fluid into the blood vessel”. It is now thought that this mechanism is incorrect and that a ruptured plaque does not release materials into the bloodstream but causes a thrombus to form at the site of rupture. This mechanism is described by Muller, “Presentation at Cardiovascular Revascularization Therapies”, Mar. 28-31, 2005, Washington D.C., and by Fuster et al, “Atherothrombosis and High Risk Plaque”, Journal of the American College of Cardiology, 2005, Vol. 46, No. 6, pp. 937-54.
There is currently no effective cryoenergy based method to treat unstable plaque that has or is likely to rupture.
Many of the known cryocatheters have safety limitations. Typically, the catheter will use a phase change Joule Thomson refrigerant system in which liquid refrigerant transforms into a gas which inflates the catheter balloon. This system carries with it an inherent risk of gas leakage causing serious harm or death due to emboli. A typical device with such inherent risks is described in U.S. Pat. No. 6,908,462.
Additionally, the catheter in many devices employs a double balloon structure which causes an increase in bulk and diameter compared to smaller designs. The double balloon structure is used to place insulation between the balloons in order to achieve a correct target temperature, as is described in U.S. Pat. No. 6,514,255. A double balloon structure may also be used to mitigate safety concerns caused from gas leaks such as those described above. The increase in bulk and diameter makes the double balloon type design more difficult to develop a clinically acceptable design for small diameter arteries such as in the coronary or smaller peripheral vasculature where the catheter will be difficult to manoeuver.
As described above, conventional cryotreatment for cardiovascular diseases has been aimed at cryoplasty, preventing restenosis of the vessel or treating atrial fibrillation. These methods typically use a double walled balloon at a high pressure, usually to dilate the target vessel. N2O is typically used as a refrigerant which undergoes a phase change. The high pressure serves to dilate the vessel and the pressure also controls the boiling point of the refrigerant inside the inner balloon thereby to control the temperature of the N2O. There is currently no effective cryoenergy based method to treat unstable plaque that has or is likely to rupture.